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OBJECTIVES: The purposes of this study were to assess clinical and radiographic outcomes following plate-assisted bone segment transport (PABST) in large bone defects of the lower extremities. DESIGN: Retrospective study of prospectively collected data. SETTING: Level-1 trauma center located in Germany. PATIENT SELECTION CRITERIA: Patients who underwent PABST and were at least 1 year postoperatively were included. OUTCOME MEASURES AND COMPARISONS: Demographic data were collected. Radiographic apparent bone gap (RABG), time to consolidation, time to full weight-bearing, and consolidation index were calculated. Numeric rating scale, lower extremity functional scale (LEFS), and complications were assessed. RESULTS: Fifteen patients [13 male; mean age 51 years (range, 20-75)] underwent PABST and had follow-up at a mean of 29.1 months. The tibia was affected in 8 and the femur in 7 patients. Preoperative RABG was 60 mm [interquartile range (IQR): 40-125], and bone defects were caused by septic nonunions in 73% of patients. Fourteen patients (93%) demonstrated consolidated transport callus at 7.3 months [95% confidence interval (95% CI), 6-8.5], and 9 patients (60%) demonstrated complete consolidation of both docking site and transport callus at 11.5 months (95% CI, 7.3-15.3). Postoperative RABG was 0.1 mm (IQR: 0-0.8), and consolidation index was 1.9 months/cm (95% CI, 1.3-2.5). All patients achieved full weight-bearing at 8.7 months (IQR: 6.5-10.3). LEFS was 42 (95% CI, 34-50), and numeric rating scale was 3 (95% CI, 2-4). Patients treated for tibial defects had a significantly higher consolidation rate compared with patients treated for femoral defects ( P = 0.040). CONCLUSIONS: PABST demonstrated high consolidation of transport callus with few complications. Although full weight-bearing was achieved in all patients, complete consolidation of the docking site was only present in 60% of cases. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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Tibia , Fracturas de la Tibia , Humanos , Masculino , Persona de Mediana Edad , Tibia/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Fémur/cirugía , Extremidad Inferior , Fracturas de la Tibia/cirugíaRESUMEN
The treatment of non-unions is often complicated by segmental bone defects and bacterial colonization. Because of the limited availability of autologous bone grafts, tissue engineering focuses on antibiotic-loaded bone graft substitutes. HACaS+G is a resorbable calcium sulphate-hydroxyapatite loaded with gentamicin. The osteoinductive, osteoconductive, and anti-infective effect of HACaS+G has already been demonstrated in clinical studies on patients with chronic osteomyelitis. However, especially for the treatment of infected non-unions with segmental bone defects by HACaS+G, reliable clinical testing is difficult and sufficient experimental data are lacking. We used an already established sequential animal model in infected and non-infected rat femora to investigate the osteoinductive, osteoconductive, and anti-infective efficacy of HACaS+G for the treatment of infected non-unions. In biomechanical testing, bone consolidation could not be observed under infected and non-infected conditions. Only a prophylactic effect against infections, but no eradication, could be verified in the microbiological analysis. Using µ-CT scans and histology, osteoinduction was detected in both the infected and non-infected bone, whereas osteoconduction occurred only in the non-infected setting. Our data showed that HACaS+G is osteoinductive, but does not have added benefits in infected non-unions in terms of osteoconduction and mechanical bone stability, especially in those with segmental bone defects.
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The treatment of infected and non-infected non-unions remains a major challenge in trauma surgery. Due to the limited availability of autologous bone grafts and the need for local anti-infective treatment, bone substitutes have been the focus of tissue engineering for years. In this context, bioactive glasses are promising, especially regarding their anti-infective potential, which could reduce the need for local and systemic treatment with conventional antibiotics. The aim of this study was to investigate the osteoinductive and osteoconductive effects, as well as the anti-infectious potential, of S53P4 using a standardized non-union model, which had not been investigated previously. Using an already established sequential animal model in infected and non-infected rat femora, we were able to investigate bioactive glass S53P4 under realistic non-union conditions regarding its osteoinductive, osteoconductive and anti-infective potential with the use of µCT scans, biomechanical testing and histological, as well as microbiological, analysis. Although S53P4 did not lead to a stable union in the non-infected or the infected setting, µCT analysis revealed an osteoinductive effect of S53P4 under non-infected conditions, which was diminished under infected conditions. The osteoconductive effect of S53P4 remained almost negligible in histological analysis, even 8 weeks after treatment. Additionally, the expected anti-infective effect could not be demonstrated. Our data suggested that S53P4 should not be used in infected non-unions, especially in those with large bone defects.
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Non-unions continue to present a challenge to trauma surgeons, as current treatment options are limited, duration of treatment is long, and the outcome often unsatisfactory. Additionally, standard treatment with autologous bone grafts is associated with comorbidity at the donor site. Therefore, alternatives to autologous bone grafts and further therapeutic strategies to improve on the outcome and reduce cost for care providers are desirable. In this study in Sprague-Dawley rats we employed a recently established sequential defect model, which provides a platform to test new potential therapeutic strategies on non-unions while gaining mechanistic insight into their actions. The effects of a combinatorial treatment of a bone graft substitute (HACaS+G) implantation and systemic PTH administration was assessed by µ-CT, histological analysis, and bio-mechanical testing and compared to monotreatment and controls. Although neither PTH alone nor the combination of a bone graft substitute and PTH led to the formation of a stable union, our data demonstrate a clear osteoinductive and osteoconductive effect of the bone graft substitute. Additionally, PTH administration was shown to induce vascularization, both as a single adjuvant treatment and in combination with the bone graft substitute. Thus, systemic PTH administration is a potential synergistic co-treatment to bone graft substitutes.
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Sustitutos de Huesos/administración & dosificación , Fracturas no Consolidadas/terapia , Neovascularización Fisiológica/efectos de los fármacos , Hormona Paratiroidea/administración & dosificación , Animales , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Regeneración Ósea/efectos de los fármacos , Remodelación Ósea/efectos de los fármacos , Sustitutos de Huesos/farmacología , Trasplante Óseo , Sulfato de Calcio/administración & dosificación , Sulfato de Calcio/farmacología , Terapia Combinada , Combinación de Medicamentos , Durapatita/administración & dosificación , Durapatita/farmacología , Fracturas del Fémur/terapia , Gentamicinas/administración & dosificación , Gentamicinas/farmacología , Receptores de Lipopolisacáridos/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: The treatment of fracture- or non-union-related infections has persistently been a major challenge for both patients and treating surgeons. With rising aging of patients and increasing comorbidities, combined with the heterogeneity of germs and any number of multi-resistance against standard antibiotics, a successful treatment is increasingly difficult. One potential solution could be a custom-made individualized antibacterial coating of standard implants with a biphasic degradable biocarrier (Cerament G/V, supplied by Bonesupport AB, Lund, Sweden) that releases high doses of antibiotics around the bone-implant-interface. Here, we describe our technique of coating intramedullary nails, plates and press-fit shoulder endoprostheses which may prevent bacterial adhesion and biofilm formation. So far, there is very limited experience in individual coating of implants in hip or knee endoprostheses to prevent reoccurrence of surgical-site infection. Currently, no reports are available for coating of stems of shoulder prosthesis and nails or plates for fracture fixation. METHODS: Here, we show our first experiences with a new individualized surgical technique of coating these implants with a resorbable antibiotic-loaded hydroxyapatite/calcium sulphate biocomposite to prevent biofilm formation and thereby recurrence of bone or joint infection. We describe three cases for coating of plates and nails for fracture fixation and coating of stems of a shoulder prosthesis. RESULTS: No adverse events of the resorbable bone graft substitute were observed. In all of the cases, no recurrence of the infection was observed and osseointegration was achieved. After implant coating of the shoulder prosthesis, no radiological signs of loosening were detected. CONCLUSION: We present a new surgical approach of a surface coating of plates, intramedullary nails or prostheses. The osteoconductive- and anti-inflammatory effect of the gentamicin- or vancomycin-loaded hydroxyapatite/calcium sulphate bone graft substitutes shows promising results.
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BACKGROUND: The treatment of fracture-related infections (FRI) is still a challenge for orthopedic surgeons. The prevalence of FRI is particularly high in open fractures with extensive soft-tissue damage. This study aimed to develop a new two-step animal model for non-unions with segmental bone defects, which could be used to evaluate new innovative bone substitutes to improve the therapeutic options in humans with FRI and bone defects. METHODS: After randomization to infected or non-infected groups, 30 Sprague-Dawley rats underwent a transverse osteotomy of the mid-shaft femur with a 5 mm defect. Additionally, the periosteum at the fracture zone was cauterized at both sides. After intramedullary inoculation with 103 CFU Staphylococcus aureus (infected group) or PBS (non-infected group), a fracture stabilization was done by intramedullary K-wires. After 5 weeks, the bone healing process was evaluated, and revision surgery was performed in order to obtain increased bone healing. The initial K-wires were removed, and debridement of the osteotomy-gap was done followed by a more stable re-osteosynthesis with an angle-stable plate. After further 8 weeks all rats were euthanized and the bone consolidation was tested biomechanically and the callus formation quantitatively by micro-CT analysis. RESULTS: We developed and presented a new two-stage non-union animal model through a targeted S. aureus infection. After 5 weeks, all animals showed a non-union irrespective of assignment to the infected and non-infected group. Lane and Sandhu score showed a higher callus formation in the infected group. In all infected animals, the inoculated S. aureus strain was detected in the revision surgery. The second surgery did not improve bone healing, as shown by the Lane Sandhu score and in the µ-CT analysis. Similarly, biomechanical testing showed in both groups a significantly lower maximum torque as compared to the contralateral side (p < 0.0001). CONCLUSIONS: We were able to successfully develop a new two-stage non-union animal model, which reflects a genuine clinical situation of an infection-related non-union model with segmental bone defects. This model could be used to evaluate various therapeutic anti-infectious and osteoinductive strategies in FRIs.
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Fracturas del Fémur/cirugía , Curación de Fractura/fisiología , Fracturas no Consolidadas/cirugía , Osteítis/complicaciones , Infecciones Estafilocócicas/complicaciones , Animales , Modelos Animales de Enfermedad , Femenino , Fijación Interna de Fracturas , Osteítis/microbiología , Distribución Aleatoria , Ratas , Ratas Sprague-DawleyRESUMEN
Implantation of mesenchymal stroma cells (MSCs) is an attractive approach to stimulate closure of large bone defects but an optimal carrier has yet to be defined. MSCs may display trophic and/or immunomodulatory features or stimulate bone healing by their osteogenic activity. The aim of this study was to unravel whether fibrin hydrogel supports early actions of implanted MSCs, such as host cell recruitment, immunomodulation and tissue regeneration, in long bone defects. Female rats received cell-free fibrin or male MSCs embedded in a fibrin carrier into plate-stabilized femoral bone defects. Removed callus was analyzed for host cell invasion (day 6), local cytokine expression (days 3 and 6) and persistence of male MSCs (days 3, 6, 14 and 28). Fibrin-MSC composites triggered fast attraction of host cells into the hydrogel while cell-free fibrin implants were not invaded. A migration front dominated by M1 macrophages and endothelial progenitor cells formed while M2 macrophages remained sparse. Only MSC-seeded fibrin hydrogel stimulated early tissue maturation and primitive vessel formation at day 6 in line with significantly higher VEGF mRNA levels recorded at day 3. Local TNF-α, IL-1ß and IL-10 expression indicated a balanced immune cell activity independent of MSC implantation. Implanted MSCs persisted until day 14 but not day 28. Our results demonstrate that fibrin hydrogel is an attractive carrier for MSC implantation into long bone defects, supporting host cell attraction and pro-angiogenic activity. By this angiogenesis, implant integration and tissue maturation was stimulated in long bone healing independent of long-term engraftment of implanted MSCs.